Could MRONJ Be Related to Osimertinib Monotherapy in Lung Cancer Patients after Denosumab Suspension?

BACKGROUND: Medication-related osteonecrosis of the jaws is the most frequent complication in patients treated or in therapy with antiresorptive/antiangiogenetic drugs. The list of medications possibly related to MRONJ onset is constantly growing; we aimed to report on a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (Osimertinib) as possibly responsible for bilateral maxillary necrosis onset in the herein-described case. METHODS: In June 2023, an oncologic patient with two different maxillary bone exposures was referred to our attention. His medical history revealed a two-year Denosumab regimen along with Osimertinib, the latter not suspended before teeth extractions. The clinicians performed a sequestrum removal and bone debridement after three cycles of antibiotic therapy. RESULTS: Histologic examinations confirmed the clinical diagnosis of MRONJ excluding a metastatic occurrence, while complete mucosal healing was achieved after 15 days. CONCLUSIONS: The patient suspended Denosumab for more than six months before teeth extraction for MRONJ prevention; hence, failure to discontinue Osimertinib led us to consider it a possible etiological factor. From a literature analysis, only one case has already been published reporting a possible Osimertinib-related occurrence of MRONJ in lung cancer patients. Our case is a further report that could be intended as an alert both for oncologists and dentists to share decisions about the oral management of such patients together, also informing them about this possible risk. Also, this report could trigger in the scientific community the necessity to evaluate further guidelines for similar doubtful cases in which the drug interaction, the mono-suspension, and the possible removable prosthesis-related additional trauma should be considered causes or con-causes.

The Effect of a Zinc-L-Carnosine Mouthwash in the Management of Oral Surgical Wounds: Preliminary Results of a Prospective Cohort Study.

BACKGROUND: Zinc L-carnosine promotes the transition from the inflammatory to the proliferative phase of wound healing by reducing the expression of pro-inflammatory signals and enhancing the expression of anti-inflammatory signals. This prospective cohort study aims to test the effect of a zinc-L-carnosine mouthwash in promoting oral surgical wound healing. METHODS: From October 2022 to February 2023, the authors enrolled healthy adult volunteers who needed the extraction of bilateral molars at the Unit of Dentistry of the University of Bari. The authors studied the baseline wound healing of each patient after the first extraction. Three months later, the patients underwent the second extraction and rinsed their mouths with zinc-L-carnosine mouthwash twice per day for the following 28 postoperative days. For a month after each extraction, the patients received weekly follow-up visits by an oral surgeon blinded about the study to record the modified healing index score of the wounds (range 0-6 points). For statistical analysis, we used the one-tailed t-test for paired samples with a significance level set at p < 0.05 to compare the baseline scores with those recorded during the exposure to the zinc-L-carnosine mouthwash. RESULTS: The authors enrolled four women and six men (mean age = 44.60 ± 19.22 years). On the seventh and fourteenth postoperative days, the mean difference between the modified healing index scores obtained by using the zinc-L-carnosine mouthwash and the baseline was not significant. On the twenty-first postoperative day, the mean score obtained by using the mouthwash was 5.2 ± 1.3 points and was significantly higher than the 4.7 ± 1.8 points of the baseline (p = 0.026). On the twenty-eighth postoperative day, the mean difference was significant as well (5.9 ± 0.3 points and 5.4 ± 1.1 points, respectively). CONCLUSION: The preliminary results of this study showed that the zinc-L-carnosine mouthwash improved the quality of oral surgical wound healing.

Targeted Diode Laser Therapy for Oral and Perioral Capillary-Venous Malformation in Pediatric Patients: A Prospective Study.

BACKGROUND: This study describes the management protocol for capillary-venous malformations in pediatric patients and reports the epidemiology of diagnosed and treated cases at the Unit of Odontostomatology of the Aldo Moro University of Bari from 2014 to 2022. METHODS: The authors classified the intraoral and perioral capillary-venous malformations by superficial diameter (<1 cm, 1-3 cm, >3 cm) and ultrasonographical depth extension (≤5 mm, >5 mm). All patients underwent pulsed-mode diode laser transmucosal photocoagulation (8-12 W/cm2); those with malformations that were wide (>3 cm) and deep (>5 mm) received intralesional photocoagulation, too (13 W/cm2). The children received general anesthesia based on their compliance and lesions' extension. The follow-up lasted six months. RESULTS: A total of 22 females and 14 males (age range 4-18 years) presented 63 capillary-venous malformations. Five patients with Sturge-Weber syndrome, seven with hereditary hemorrhagic telangiectasia, and five with angiomatosis showed multiple malformations. The authors found no intraoperative or postoperative complications. Seventeen patients with lesions >1 cm and >5 mm deep required multiple laser sessions to heal. CONCLUSION: The results of the current study support diode laser photocoagulation as the gold standard for the treatment of intraoral and perioral capillary-venous malformations in pediatric patients.

Effect of Preoperative Music Therapy Versus Intravenous Midazolam on Anxiety, Sedation and Stress in Stomatology Surgery: A Randomized Controlled Study.

BACKGROUND: Patients undergoing surgery and general anesthesia often experience anxiety, fear and stress, with negative bodily responses. These may be managed by the pre-procedural application of anxiolytic, analgesic, and anesthetic drugs that have, however, potential risks or side effects. Music therapy (MT) can be used as a complementary no-drug intervention alongside standard surgical care before, during and after medical procedures. The aim of this study was to evaluate the effects of preoperative MT intervention compared to premedication with midazolam on levels of anxiety, sedation and stress during general anesthesia for elective stomatology surgery. METHODS: A two-arm randomized and controlled single-center, parallel-group, pre-post event study was conducted. In total, 70 patients affected by stage I or II (both clinically and instrumentally N0) micro-invasive oral cancer and undergoing elective surgery under general anesthesia were assigned to the control group (CG) or to the music therapy group (MTG). MTG patients received preoperative music therapy intervention (MT) from a certified music therapist before surgery, while the CG patients did not receive MT but instead received premedication with intravenous midazolam, 0.02 mg/kg. Anesthesia was the same in both groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were recorded at the entrance to the operating room, just before the induction of anesthesia and every 5 min until the end of surgery. An anxiety visual analogues scale (A-VAS) was used to evaluate the level of anxiety. The bispectral index (BIS) monitor was used to measure the depth of sedation just before and 10 min after both music intervention and midazolam administration. Stress response was assessed 5 min before and 20 min after surgery via the control of plasma prolactin (PRL), growth hormone (GH), and cortisol levels. The patient global impression of satisfaction (PGIS) was tested 1 h after surgery. Participants in the MTG were asked to answer 3 questions concerning their experience with MT. RESULTS: No statistical differences among the PRL, GH and cortisol levels between the two groups were registered before and after the treatment, as well as for PAS, PAD and HR. Significant differences in the A-VAS scores between the MTG and CG (p < 0.01) was observed. Compared to the CG, MTG patients had a statistically significantly lower BIS score (p = 0.02) before induction. A PGIS score of 86.7% revealed that patients in the MTG were very satisfied, versus 80% in the CG (p < 0.05). CONCLUSION: Preoperative music therapy could be an alternative to intravenous midazolam when aiming to promote a preoperative and post-operative state of anxiolysis and sedation in stomatology surgery, even if no differences were found in terms of the surgery-related stress response according to physiological and hormonal determinations.

Oral lichen planus in children: An Italian case series.

Oral lichen planus usually occurs in adults; there are no clear data regarding the incidence and the clinical features of oral lichen planus in children. This paper reports clinical findings, treatments, and outcomes of 13 Italian patients with oral lichen planus in childhood diagnosed between 2001 and 2021. The most common finding was keratotic lesions with reticular or papular/plaque-like patterns, confined to the tongue in seven patients. Although oral lichen planus in childhood is rare and the malignant transformation index is unknown, specialists must be aware of its characteristics and oral mucosal lesions must be correctly diagnosed and managed.

Oral lesions with immunohistochemical evidence of Sars-CoV-2 in swab-negative post-COVID syndrome.

OBJECTIVES: Growing evidence exists about post-COVID condition/syndrome as sequelae of Sars-CoV-2 infection in healed patients, possibly involving the lungs, brain, kidney, cardiovascular and neuromuscular system, as well the persistency of taste dysfunction. Such symptoms develop during or after infection and continue for more than 12 weeks with pathogenesis related to virus persistency but variable by organs or systems. MATERIALS AND METHODS: We recently observed six patients recovered from COVID-19 and with negative RT-PCR testing, showing oral mucosa lesions (mainly ulcers) overlapping those occurring in the acute phase, persisting up to 20 days and thus needing a biopsy with histological investigation and spike protein evaluation by immunohistochemistry. RESULTS: We found epithelial ulceration, inflammatory infiltrate, vessels with increased diameter and flattened endothelium but no thrombi formation; also, we found a weak epithelial SARS-CoV-2 positivity limited to the basal/spinosum layers, progressively decreasing toward the periphery, and the intraepithelial lymphomonocytes, endothelium, and perivascular pericytes too. CONCLUSIONS: Our findings provide evidence that SARS-CoV-2 can persist, as for other organs/systems, also in the oral epithelium/mucosa after the acute phase and can be responsible for lesions, although by a pathogenetic mechanism that should be better defined but certainly referable as the oral mucosa counterpart of post-COVID syndrome.

Metastatic Lung Cancer to the Head and Neck: A Clinico-Pathological Study on 21 Cases with Narrative Review of the Literature.

Metastases from lung cancer to the oral cavity and to the head and neck generally are very infrequent and usually manifest in advanced stages of the disease. Even more rarely, they are the first sign of an unknown metastatic disease. Nevertheless, their occurrence always represents a challenging situation both for clinicians, in the management of very unusual lesions, and for pathologists, in the recognition of the primary site. We retrospectively studied 21 cases of metastases to the head and neck from lung cancer (sixteen males and five females, age range 43-80 years; eight cases localized to the gingiva [two of these to the peri-implant gingiva], seven to the sub-mandibular lymph nodes, two to the mandible, three to the tongue, one case to the parotid gland; in eight patients, metastasis was the first clinical manifestation of an occult lung cancer) and proposed a wide immunohistochemical panel for a proper identification of the primary tumor histotype, including CK5/6, CK8/18, CK7, CK20, p40, p63, TTF-1, CDX2, Chromogranin A, Synaptophysin, GATA-3, Estrogen Receptors, PAX8, PSA. Furthermore, we collected data from previously published studies and narratively reviewed the relevant literature.

Osteoma of the Jaw as First Clinical Sign of Gardner's Syndrome: The Experience of Two Italian Centers and Review.

Gardner's syndrome (GS) is a combination of polyposis, osteomas, fibromas, and sebaceous cysts. The aim of the study is to highlight whether maxillofacial osteoma could represent an early detection symptom of GS. Patients with suspected osteoma of the jaw underwent genetic and radiographical examinations. The database gathered 19 patients with oral osteoma that was histologically diagnosed; the whole sample was positive for APC gene mutation. Other cranial and peripheral locations were reported. Osteoma of the jaw is a crucial predictive factor of GS, and dentists and oral and maxillofacial surgeons must be aware of the importance of a timely diagnosis.

Medication-related osteonecrosis of the jaw triggered by endodontic failure in oncologic patients.

OBJECTIVES: To describe the association between endodontic treatment failure and medication-related osteonecrosis of the jaw (MRONJ) in a cohort of oncologic patients in therapy with antiresorptive and antiangiogenic drugs. MATERIALS AND METHODS: Patients were selected as affected by MRONJ in absence of the common local risk factors (oral surgical procedures or ill-fitting dentures) but showing failure of previous endodontic treatment performed at least 6 months before the starting of antiresorptive/antiangiogenic therapies. Jaw lesions were all surgically treated and patients underwent a strict clinical and radiological follow-up. RESULTS: Among 18 patients, who developed 18 MRONJ, the only detectable local risk factor was the presence of teeth with failed endodontic treatment (more precisely, root canal underfilling in eight cases, root canal overfilling in two cases, root perforation in three cases, root fracture in five cases). All patients completely healed after surgical procedure and no recurrence was observed. CONCLUSIONS: Endodontic treatment failure should be considered a local risk factor for MRONJ development in oncologic patients. For such reason, it is mandatory to carefully evaluate them prior than the beginning of antiresorptive and antiangiogenic drugs administration.

Lingual laser frenotomy in newborns with ankyloglossia: a prospective cohort study.

BACKGROUND: The study aims to describe the lingual laser frenotomy perioperative protocol for newborns with ankyloglossia with or without breastfeeding difficulties developed by Odontostomatology and Neonatology and Neonatal Intensive Care Units of the Aldo Moro University of Bari. METHODS: Authors carried out a prospective observational cohort study. Newborns with ankyloglossia (classified by using both Coryllos' and Hazelbaker's criteria) with or without difficult breastfeeding (according to Infant Breastfeeding Assessment Tool) underwent diode laser frenotomy (800 ± 10 nm; 5 W; continuous wave mode; contact technique; under topical anesthesia) and follow-up visits after seven and thirty days postoperatively. The authors analyzed as main outcomes the perioperative pain intensity measured by the C.R.I.E.S. scale, the occurrence of complications and quality of healing, the quality of breastfeeding, newborn's postoperative weight gain, maternal nipple pain, and the presence of lesions as secondary outcomes. RESULTS: Fifty-six newborns were included in the current study. Intraoperative mean pain intensity was 5.7 ± 0.5 points, resolved within thirty postoperative minutes. Observed complications were mild punctuating bleeding, carbonization of the irradiated site, and transitory restlessness. All wounds were completely healed within the thirtieth postoperative day. During follow-up, a significant breastfeeding improvement was evident with satisfactory newborns' weight gain and a significant reduction of nipple pain and lesions (p < .05). CONCLUSION: Our lingual laser frenotomy protocol provided significant breastfeeding improvement in the mother-newborn dyads with low intraoperative pain and no significant complications.

The New Era of Salivaomics in Dentistry: Frontiers and Facts in the Early Diagnosis and Prevention of Oral Diseases and Cancer.

Nowadays, with the development of new and highly sensitive, blood is not the only medium of choice for the diagnosis of several diseases and pathological conditions. Saliva is now considered a safe and non-invasive sample to study oral and systemic diseases, showing great diagnostic potential. According to several recent studies, saliva has emerged as an emerging biofluid for the early diagnosis of several diseases, indicated as a mirror of oral and systemic health and a valuable source of clinically relevant information. Indeed, several studies have observed that saliva is useful for detecting and diagnosing malignant tumours, human immunodeficiency virus, heart disease, and autoimmune diseases. The growing realisation that saliva is an inexhaustible source of information has led to the coining of the term 'Salivaomics', which includes five "omics" in connection with the main constituents of saliva: genome and epigenome, transcriptomics, metabolomics, lipidomics, proteomics and microbiota. All those may be changed by disease state, so they offer significant advantages in the early diagnosis and prognosis of oral diseases. The aim of the present review isto update and highlight the new frontiers of salivaomics in diagnosing and managing oral disorders, such as periodontitis, premalignant disorders, and oral squamous cell carcinoma (OSCC).

Peri-Implant Metastasis as First Manifestation of an Unknown Lung Cancer: Literature Review and Two New Cases.

Metastases around dental implants are extremely rare. They usually represent a secondary localization of a multiorgan metastatic neoplasm but also are, exceptionally, recognized as the first clinical manifestation of a still unknown cancer of whatever organ. Metastases usually manifest as rapidly growing lesions of hard and soft tissues and always represent a true diagnostic/therapeutic dilemma both for clinicians in choosing the more appropriate treatment and for pathologists in recognizing the primary tumor when still undiagnosed. We report 2 distinct cases of metastasis occurring around dental implants in the maxilla and mimicking peri-implantitis at the onset; more precisely, in one case, the lesion involved exclusively the alveolar bone, where an implant were previously inserted, while in the other case, a neoplasm caused bone destruction around the fixture with an impressive and rapid exophytic growth. In both cases, maxillary lesions were the first metastatic manifestation of an unknown adenocarcinoma of the lung.

Peri-implantitis-like medication-related osteonecrosis of the jaw: Clinical considerations and histological evaluation with confocal laser scanning microscope.

OBJECTIVE: In the recent years, an increasing number of peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ) have been reported in literature, both in oncologic and osteoporotic patients. The aim of this study is to describe 19 cases of patients previously diagnosed as affected by peri-implantitis, who were treated for PI-MRONJ, with consideration on clinical and histopathological features. MATERIALS AND METHODS: Patients included were affected by postmenopausal osteoporosis and were administered with different antiresorptive drugs. Due to the presence of clinical and radiological signs of peri-implantitis not healed after non-surgical periodontal treatment, they were referred to the Complex Operating Unit of Odontostomatology of the University of Bari. Then, after a drug holiday of at least 3 months and cycles of antibiotics, and after other cycles of periodontal treatment, patients underwent the surgical removal of implant fixtures and surrounding bone. RESULTS: Although the previous diagnosis of peri-implantitis, the histopathological analysis with both conventional and confocal laser scanner microscopy confirmed the diagnosis of peri-implantitis-like MRONJ. CONCLUSION: Peri-implantitis not healed after conventional treatment in patients at risk on MRONJ occurrence should be considered as peri-implantitis-like PI-MRONJ and treated as required in order to get complete healing of the pathological condition, thus avoiding delay in the diagnosis.

Brugada Syndrome Updated Risk Assessment and Perioperative Management in Oral Surgery: A Case Series.

Brugada syndrome (BrS) carries the risk of major dysrhythmias increased further by exposure to pro-dysrhythmic factors related to oral surgical procedures such as local anesthetics, anxiety, and postoperative pain. Such risk can be handled by updated multidisciplinary management. In 2020, 3 male BrS patients needed oral surgical treatments at the Complex Unit of Odontostomatology of Aldo Moro University of Bari, Italy. Multidisciplinary individual risk assessment involved cardiologic hazard ratio stratification, event-free survival stratification, and 5-year average risk of ventricular dysrhythmias and sudden cardiac death for Brugada patients; American Society of Anesthesiologists physical status risk class; expected complexity and duration of the procedure; and anxiety score measured by the Modified Dental Anxiety Scale. The authors administered conscious sedation by intravenous diazepam to both a patient susceptible to vasovagal syncope needing tooth extraction with concomitant cystectomy (longer-lasting procedure) and to another who needed routine tooth extraction (brief procedure) but had a moderate dental anxiety score; the last 1 received local anesthesia alone due to his low anxiety, low susceptibility to vasovagal syncope, and need for routine tooth extraction. After positioning external biphasic defibrillator pads, 12-leads continuous electrocardiogram, and peripheral venous access, extractions were performed with local anesthesia by lidocaine 2% with epinephrine 1:100,000; acetaminophen was suggested for postoperative analgesia. No electrocardiographic changes occurred in the perioperative period. The current multidisciplinary individual risk assessment allowed us to detect each BrS patient's risk factors for major dysrhythmias and to adapt oral surgical and anesthesiologic protocols for safe targeted treatment.

Oral and Maxillo-Facial Manifestations of Systemic Diseases: An Overview.

Many systemic (infective, genetic, autoimmune, neoplastic) diseases may involve the oral cavity and, more generally, the soft and hard tissues of the head and neck as primary or secondary localization. Primary onset in the oral cavity of both pediatric and adult diseases usually represents a true challenge for clinicians; their precocious detection is often difficult and requires a wide knowledge but surely results in the early diagnosis and therapy onset with an overall better prognosis and clinical outcomes. In the current paper, as for the topic of the current Special Issue, the authors present an overview on the most frequent clinical manifestations at the oral and maxillo-facial district of systemic disease.

Covid-19 Symptomatic Patients with Oral Lesions: Clinical and Histopathological Study on 123 Cases of the University Hospital Policlinic of Bari with a Purpose of a New Classification.

The aim of this study is to report on the oral lesions detected in 123 patients diagnosed at the University Hospital of Bari from October 2020 to December 2020, focusing on the correlation of clinical and pathological features in order to purpose a new classification. METHODS: General and specialistic anamnesis were achieved and oral examination was performed. The following data were collected: age/gender, general symptoms and form of Covid-19, presence and features of taste disorders, day of appearance of the oral lesions, type and features of oral lesions and day of beginning of therapies. If ulcerative lesions did not heal, biopsy was performed. RESULTS: Many types of oral lesions were found and classified into four groups considering the timing of appearance and the start of the therapies. Early lesions in the initial stages of Covid-19 before the start of therapies was observed in 65.9% of the patients. In the histopathological analysis of four early lesions, thrombosis of small and middle size vessels was always noticed with necrosis of superficial tissues. CONCLUSION: The presence of oral lesions in early stages of Covid-19 could represent an initial sign of peripheral thrombosis, a warning sign of possible evolution to severe illness. This suggests that anticoagulant therapies should start as soon as possible.

Diode Laser Management of Primary Extranasopharyngeal Angiofibroma Presenting as Maxillary Epulis: Report of a Case and Literature Review.

Juvenile nasopharyngeal angiofibroma is a rare vascular neoplasm, mostly occurring in adolescent males, and representing 0.05% of all head and neck tumors. Nevertheless, it is usually recognized as the most common benign mesenchymal neoplasm of the nasopharynx. Usually, it originates from the posterolateral wall of the nasopharynx and, although histologically benign, classically shows a locally aggressive behavior with bone destruction as well as spreading through natural foramina and/or fissures to the nasopharynx, nasal and paranasal cavities, spheno-palatine foramen, infratemporal fossa and, very rarely, to the cranial cavity. Extranasopharyngeal angiofibroma is considered a distinct entity due to older age at presentation, different localizations (outside the nasopharyngeal pterygopalatine fossa) and attenuated clinical course. Extranasopharyngeal angiofibroma has been sporadically described in the oral cavity. We report a case of extranasopharyngeal angiofibroma with primary and exclusive involvement of the adherent gingiva of the anterior maxilla, managed by preoperative diode laser trans-mucosal photocoagulation and subsequent surgical removal. The current literature on primary extranasopharyngeal angiofibroma is also reviewed.

Peripheral Giant Cell Granuloma of the Jaws as First Sign of Primary Hyperparathyroidism: A Case Series.

Peripheral giant cell granulomas (PGCG) associated with hyperparathyroidism (HPT) are rare clinical entities. The aim of this study is to report on 21 PGCGs of the oral cavity as the first clinical sign of unknown primary HPT (PHPT) referred to the Complex Operating Unit of Odontostomatology of Aldo Moro University of Bari from 2009 to 2019. Surgical treatment consisted in conservative enucleation of the lesion, if possible, with contextual bone rim osteoplasty with piezosurgical tools and following histological examination. After histological diagnosis of PGCG, PHPT screening was performed dosing parathyroid hormone and serum calcium. In all the patients haematological investigation demonstrated elevated values of parathyroid hormone and serum calcium ruling out an unknown PHPT. Specifically, after endocrinological evaluation, patients showed PHPT related to: parathyroid adenoma (13), parathyroid hyperplasia (two, one of which occurred in a intra-thyroidal parathyroid), and parathyroid carcinoma (1) and were scheduled for surgical treatment. Considering that PGCGs could represent the first clinical sign of an undiagnosed PHPT and the screening of PHPT is a non-invasive and cheap exam, in case of histological diagnosis of a giant cell lesion, both central and peripheral, especially in patients with synchronous or history of methacronous giant cell lesions, parathyroidal screening should be mandatory.

Primary Breast Extranodal Marginal Zone Lymphoma in Primary Sjögren Syndrome: Case Presentation and Relevant Literature.

The association between autoimmune diseases, mostly rheumatoid arthritis, systemic lupus erythematosus, celiac disease and Sjögren syndrome, and lymphoma, has been widely demonstrated by several epidemiologic studies. By a mechanism which has not yet been entirely elucidated, chronic activation/stimulation of the immune system, along with the administration of specific treatments, may lead to the onset of different types of lymphoma in such patients. Specifically, patients affected by Sjögren syndrome may develop lymphomas many years after the original diagnosis. Several epidemiologic, hematologic, and histological features may anticipate the progression from Sjögren syndrome into lymphoma but, to the best of our knowledge, a definite pathogenetic mechanism for such progression is still missing. In fact, while the association between Sjögren syndrome and non-Hodgkin lymphoma, mostly extranodal marginal zone lymphomas and, less often, diffuse large B-cell, is well established, many other variables, such as time of onset, gender predilection, sites of occurrence, subtype of lymphoma, and predictive factors, still remain unclear. We report on a rare case of primary breast lymphoma occurring three years after the diagnosis of Sjögren syndrome in a 57-year-old patient. The diagnostic work-up, including radiograms, core needle biopsy, and histological examination, is discussed, along with emerging data from the recent literature, thus highlighting the usefulness of breast surveillance in Sjögren syndrome patients.

Primary Oro-Facial Manifestations of Langerhans Cell Histiocytosis in Pediatric Age: A Bi-Institutional Retrospective Study on 45 Cases.

AIMS: Langerhans Cell Histiocytosis is a rare hematologic disorder usually affecting children and most commonly involving the head and neck region. Primary oro-facial manifestations are rare, and their diagnosis is often challenging as they are numerous and often resemble common pathologies, refractory to conventional medical and/or instrumental treatments. For such reasons, the diagnosis is frequently delayed, as is the following staging and therapy onset. We retrospectively studied 45 pediatric patients affected by Langerhans Cell Histiocytosis with onset in the head and neck, to examine their clinical and radiological features at the early stage. MATERIALS AND METHODS: The study was a retrospective bi-institutional analysis (Department of Pediatric Dentistry and Pediatric Oncology of "Sapienza" University of Rome, Department of Interdisciplinary Medicine of the University of Bari "Aldo Moro"), which enrolled 45 patients (age range 0-18 year-old) affected by Langerhans Cell Histiocytosis with oro-facial onset. Data regarding clinical appearance, number, site, synchronous or metachronous occurrence, involved tissues/organs, radiographic features and clinical outcomes were collected, listed and overall differentiated by two age ranges (0-10-year-olds and 10-18-year-olds). RESULTS: Patients were 26 males and 19 females, with an average age at the time of diagnosis of 4.8 ± 3.8 years (median = 3.9 years). The most common findings were inflamed, hyperplastic, painful and often ulcerated gingival lesions (22 cases), associated with deciduous tooth mobility and/or dislocation with bone loss in 18 cases, followed by nine single eosinophilic granulomas of the mandible and two of the maxilla. Lesions of the palatal mucosa were observed in six patients; nine patients showed on radiograms the characteristic "floating teeth" appearance in the mandible with synchronous lesions of the maxilla in six. Paresthesia was relatively un-frequent (three cases) and the pathological fracture of the mandible occurred in six. Head/neck lymph nodes involvement was associated with oral lesions in 12 cases and skull lesions in 14. Otitis (media or externa) was detected in four instances, exophthalmia in two, cutaneous rush in nine, contextual presence or subsequent onset of insipidus diabetes in eight. As for therapy, single or multiple small jaw lesions were all surgically removed; chemotherapy with vinblastine alone or associated with corticosteroids was the principal treatment in almost the 80% of cases; more than 50% of patients received corticosteroids, while only three patients received adjunctive radiotherapy. The overall mortality account for less than 9% (four of 45 cases) and recurrence observed in eight patients after therapy. CONCLUSIONS: Langerhans Cell Histiocytosis may mimic several oro-facial inflammatory and neoplastic diseases. Considering the potential disabling sequela following head and neck localization of Langerhans Cell Histiocytosis in children, especially at the periodontal tissues with teeth and alveolar bone loss, lesion recognition along with the histological examination of suspicious tissues is mandatory to achieve an early diagnosis and to prevent further organ involvement.